Determining the correct structure

Robert Burns Woodward at Harvard University.

We live in a world that is dictated to a large extent by the structure of things. From atoms to our universe, or even this article that you are reading at this moment, there is a certain structure that it adheres to. So it comes as no surprise that determining the structure of terramycin was crucial in its success and effectiveness as an antibiotic.

But before we get to that, we will start off with Robert Burns Woodward, a man who is considered a master in synthetic organic chemistry. Born in Boston, he grew up in poverty but displayed an aptitude for chemistry at a very young age.

While still only eight, Woodward received his first chemistry set, which he went on to improve on his own accord. This he did by gathering instructions (some of them from college level textbooks) and adding more reagents.

So when he enrolled at the Massachusetts Institute of Technology at the age of 16, his knowledge in organic chemistry was on par with the seniors in college. He did have his troubles, but in four years time, he completed both his bachelor’s degree and his doctorate.

After a stint with the University of Illinois, Woodward moved to the chemistry department in Harvard, where he stayed throughout his career. Even though he remained at the university as a faculty member, he did serve on a consultant basis with a number of companies, including Pfizer.

Organisms from soil

The quest to find organisms and harness the ability of these microscopic living creatures to fight disease was on during this time in history. Pfizer, for their part, were studying the properties of microorganisms isolated from the soil.

The Pfizer company alone screened thousands of soil samples from around the world. From ocean beds, deserts, mountains and mine shafts, these samples ranged every conceivable location on earth. The sample that mattered ended up being almost from their own backyard, from a cornfield in one of Pfizer’s Middle Western plants.

A new actinomycete named Streptomyces rimosus was revealed on investigation and the canary yellow crystals of its antibiotic were called terramycin. Terramycin, which proved to be effective against a range of diseases, was announced to the world on January 27, 1950.

Terramycin, however, posed a particular problem in that its structure could not be immediately discerned. Determining the structure became a priority, as terramycin assumed industrial significance. The overwhelming data made available by chemists only made the job even more difficult, as it became analogous to the proverbial needle search in a haystack.

Path-breaking discovery The solution, often considered one of the more brilliant analysis on a structural problem, was in the end offered by Woodward. Woodward, in fact, deduced the correct structure of terramycin through thought alone, after having taken a large piece of cardboard and listing down the important facts.

Discovering the structure of oxytetracycline (terramycin is the trade name used by Pfizer) was a breakthrough in the research of tetracycline, paving the way for derivatives, some of which still remain popular antibiotics to this day.

As for Woordward, this discovery was just one episode in a lifetime of research, which included a succession of synthesis and analyses of molecules that increasingly became more complicated (chlorophyll, cholesterol and Vitamin B12 to name a few). It didn’t go unrewarded, of course, as he went on to win the Nobel Prize in Chemistry in 1965.

Write to A.S.Ganesh at ganesh.a.s@thehindu.co.in